Safety assessment of a novel, dietary pyrroloquinoline quinone disodium salt (mnemoPQQ®)

IF 2.8 4区 医学 Q2 TOXICOLOGY Toxicology Mechanisms and Methods Pub Date : 2022-05-11 DOI:10.1080/15376516.2022.2076635
Y. Shiojima, N. Deshmukh, H. Moriyama, Yogini Soman, Prashant Nalge, Manisha Randhe, Jaideep Kanhere, Aasavari Karmarkar, M. Bagchi, D. Bagchi
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Abstract

Abstract Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid β. We developed mnemoPQQ®, a novel PQQ disodium salt and assessed its safety in GLP compliant toxicity studies. Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825- and 1410 mg/kg body weight (bw) in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. mnemoPQQ® was found to be nonirritant to the skin of rabbit in an acute dermal irritation/corrosion study, and classified mnemoPQQ® as a nonirritant to the eye of rabbit in an acute eye irritation/corrosion study. Ames bacterial reverse mutation assay and in vitro Mammalian cell gene mutation test exhibited its non-mutagenic potential. In mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic. A 90-day sub-chronic toxicity study, conducted at and up to the highest daily dose of 600 mg/kg body weight, revealed no evidence of systemic toxicity. All rats survived the treatment without any significant abnormal clinical signs and alterations in hematology, clinical chemistry, neurological evaluation, thyroid functions, reproductive hormone levels, sperm evaluations, vaginal cytology, endocrine functions, organ weight and gross and microscopic pathology findings. No observed adverse effect level (NOAEL) of mnemoPQQ® was found to be greater than 600 mg/kg body weight. These studies affirm that mnemoPQQ® has broad spectrum safety for human consumption.
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新型膳食吡咯喹啉醌二钠盐(mnemoPQQ®)的安全性评估
摘要吡咯喹啉醌(PQQ)是一种天然存在于食品中的强效辅酶抗氧化剂,已被证明可通过增强神经生长因子(NGF)和NGF受体的表达,抑制淀粉样蛋白β的原纤维形成和攻击性来保护脑细胞。我们开发了一种新型PQQ二钠盐mnemoPQQ®,并在符合GLP的毒性研究中评估了其安全性。mnemoPQQ®对Wistar大鼠的急性毒性研究表明,其LD50为1825-和1410 雄性和雌性大鼠分别为mg/kg体重,而其急性经皮LD50>2000 在一项急性皮肤刺激/腐蚀研究中发现,mg/kg bw.mnemoPQQ®对兔子皮肤无刺激性,并在一项紧急眼部刺激/腐蚀性研究中将mnemoPQQ®归类为对兔子眼睛无刺激性。Ames细菌反向突变试验和体外哺乳动物细胞基因突变试验显示其无致突变性潜力。在哺乳动物体内红细胞微核试验中,mnemoPQQ®被归类为非致裂性和非致突变性。一项为期90天的亚慢性毒性研究,以最高每日剂量600进行 mg/kg体重,没有显示出全身毒性的证据。所有大鼠在治疗后均存活,在血液学、临床化学、神经系统评估、甲状腺功能、生殖激素水平、精子评估、阴道细胞学、内分泌功能、器官重量以及大体和显微镜病理学检查结果方面均无任何显着异常临床体征和改变。未发现mnemoPQQ®的不良反应水平(NOAEL)大于600 mg/kg体重。这些研究证实,mnemoPQQ®对人类消费具有广谱安全性。
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来源期刊
自引率
3.10%
发文量
66
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.
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